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Papers In Press, published online ahead of print November 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800615-JLR200

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Journal of Lipid Research, Vol. 50, 2173-2181, November 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein^[S]

Dmitry Namgaladze, Carla Jennewein, Stefan Preiss, Andreas von Knethen and Bernhard Brüne¹

Goethe-University, Faculty of Medicine, Institute of Biochemistry I/ZAFES, 60590 Frankfurt, Germany

¹ To whom correspondence should be addressed. e-mail: bruene{at}pathobiochemie1.de

Macrophages ingesting apoptotic cells attenuate inflammatory responses, such as reactive oxygen species (ROS) generation. In atherosclerosis, ongoing inflammation and accumulation of apoptotic/necrotic material are observed, suggesting defects of phagocytes in recognizing or responding to dying cells. Modified lipoproteins such as oxidized LDL (oxLDL) are known to promote inflammation and to interfere with apoptotic cell clearance. Here, we studied the impact of cells exposed to oxLDL on their ability to interfere with the oxidative burst in phagocytes. In contrast to apoptotic cells, cells dying in response to or in the presence of oxLDL failed to suppress ROS generation despite efficiently being taken up by phagocytes. In addition, apoptotic cells, but not oxLDL-treated cells, inhibited phosphorylation of extracellular signal-regulated kinase, which is important for NADPH oxidase activation. oxLDL treatment did not interfere with activation of the antiinflammatory transcriptional regulator peroxisome proliferator-activated receptor by apoptotic cells. Moreover, cells exposed to oxLDL failed to suppress lipopolysaccharide- induced proinflammatory cytokine expression, whereas apoptotic cells attenuated these phagocyte responses. Thus, the presence of oxLDL during cell death impaired the ability of apoptotic cells to act antiinflammatory with regard to oxidative burst inhibition and cytokine expression in phagocytes.

Supplementary key words apoptosis • macrophages • NADPH oxidase • lipoproteins • phagocytosis • reactive oxygen species

Abbreviations: CMF-DA, 5-chloromethylfluorescein diacetate; ERK, extracellular signal-regulated kinase; HE, hydroethidine; IL, interleukin; MCP, mouse monocyte chemotactic protein; oxLDL, oxidized LDL; PMA, phorbol 12-myristate 13-acetate; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR response element; PS, phosphatidylserine; ROS, reactive oxygen species; TNF, tumor necrosis factor

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